DESCRIPTION: This proposal describes a program for investigating the conformations of gas-phase biomolecules and complexes. Preliminary data show that when ESI is used to produce gas-phase biomolecules, Coulombic forces that result from the multiple charges appear to be a dominant factor in establishing structure in the gas phase. In order to explore the role of noncovalent interactions in establishing structure it is proposed to develop a hybrid drift tube/time-of-flight mass spectrometer for studying high-mass/low-charge biomolecules and complexes. Questions regarding the number of different gas-phase conformations, their shapes and the connectivity between them will be addressed. Although these methods cannot give atomic detail, it is possible to extract overall shape information. The methods proposed should be fast and sensitive and make it possible to study trace amount of biological materials. The ability to study biomolecular structure in vacuum allows molecular issue that are fundamental to biochemistry, such as folding recognition, biomolecular association, and the influence of solvent on structure to be explored experimentally. The raw data will provide benchmarks for theorists who aim to calculate protein structures and dynamics in vacuo and in solution.